Identification and in silico characterization of a novel PKLR genotype in a Turkish newborn.


Canu G., De Paolis E., Righino B., Mazzuccato G., De Paolis G., Capoluongo E., ...More

Molecular biology reports, vol.47, no.10, pp.8311-8315, 2020 (Peer-Reviewed Journal) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 47 Issue: 10
  • Publication Date: 2020
  • Doi Number: 10.1007/s11033-020-05836-2
  • Journal Name: Molecular biology reports
  • Journal Indexes: Science Citation Index Expanded, Scopus, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
  • Page Numbers: pp.8311-8315

Abstract

Pyruvate kinase deficiency (PKD) is the most common glycolytic defect leading to chronic nonspherocytic hemolytic anemia (CNSHA). Clinical manifestations of PKD reflect the symptoms and complications of the chronic hemolysis, including anemia, jaundice, bilirubin gallstones due to hyperbilirubinemia, splenomegaly and iron overload. In this study, we report the finding of a 5-months-old Turkish male newborn with moderate CNSHA and PKD. Mutation screening ofPyruvate Kinase Liver/Red(PKLR)gene revealed that the patient carried the known pathogenic variant (PV)c.1456C > T(p.Arg486Trp) and an unreported variantc.1067T > G(p.Met356Arg). Computational variant analysis (CVA) highlighted the deleterious structural effects on the mutant PK enzyme, suggesting its pathogenic role. In this patient, the molecular evaluation of PKD, that allowed the identification of thenovel PKLRgenotype, coupled with CVA led to the definitive and correct diagnosis of CNSHA.